Data from the phase 2 REARRANGE study suggest flexible dosing of regorafenib may reduce certain adverse events (AEs) without affecting efficacy in patients with refractory metastatic colorectal cancer (mCRC).
REARRANGE, the largest trial to date to explore the impact of initial flexible dosing on regorafenib tolerability, randomised 299 patients to regorafenib 160 mg/day (standard dose [SD]) or 120 mg/day (reduced dose [RD]) three weeks on, one week off, or intermittent dose 160 mg one week on, one week off (intermittent dose [ID]). The safety population set was 100 (SD), 98 (RD) and 99 (ID). RD or ID was escalated to SD after cycle 1 (C1) if no limiting toxicity occurred.
The percentage of patients experiencing grade 3/4 adverse events (AE) was 60 with SD, 56 with RD and 55 with ID. Forty-five per cent of patients on RD and 64 per cent on ID were escalated to SD after C1 and the percentage starting C3 were 39 per cent (SD), 44 per cent (RD) and 35 per cent (ID). Flexible dosing was associated with numerical improvement on AEs such as fatigue, hand-foot skin reactions and hypertension.
Overall survival was 7.4, 8.6 and 7.1 months, respectively, while progression-free survival was 1.94, 2.0 and 2.0 months.